Insects and other arthropods make up over half of all described species on earth. Although the majority of these species have no immediate impact on human life, some are extremely important as disease vectors (i.e. tsetse fly, anopheline mosquitoes, triatomine bugs, ticks.), and some have developed into agricultural, forest, and household pests. Chemistry plays a central role in the interactions of insects with plants, with animal hosts, as well as with prey and predators. The aim of this project is to elucidate the chemistry underlying these interactions, based on a critical, biorational approach, in ways that should improve human health and welfare. For several hundreds of millions of years, plants and insects have been co-evolving. This interaction may be viewed as an extended biological war; the fact that much of the earth is still green bears witness to the effectiveness of plant defenses. Natural anti-feedants and repellents play important roles in plant defensive strategies. We hope to find new and potentially useful antiinsectan compounds based on our very recent discovery of secondary metabolites, which serve plants both as "nectar guides" and as anti-feeding agents. This project has the potential to reduce the agricultural use of conventional pesticides. In another project, we plan to screen a wide range of spider venoms for structurally novel neurotoxins. There are over 30,000 described species of spiders, and these ubiquitous predators are generally able to produce venoms which paralyze or kill their prey. We plan to use electrospray ionization mass spectrometry for the rapid analysis of a large number of previously unstudied spider venoms to search for novel structure types which may serve as lead compounds for new neuropharmacological agents. The discovery by an Israeli research group that female mosquitoes avoid egg laying in still water that is occupied by predatory Notonecta has exciting implications for mosquito control. The finding that this water is repellent even after the Notonecta have been removed suggests that a chemical cue is responsible for the inhibition of oviposition. We hope to characterize the responsible agents in collaboration with the Israeli group. We also plan a collaborative study of chemical communication in ticks, another important group of arthropodan disease vectors. We hope to pursue several other research problems dealing with insect chemistry. Our objectives are (I) to discover the chemical basis of important arthropod interactions, (2) to provide the basis for new control techniques which should be applicable to disease vectors and other pests, and (3) to discover new biologically active chemotypes which may serve as the starting points for synthetic projects leading to drug development or vector control.